Safety and efficacy of Yaobitong capsules for lumbar disc herniation: A multicenter, randomized, double-blinded, parallel, positive-controlled clinical trial.

BACKGROUND: Lumbar disc herniation (LDH) is one of the most common diseases and is a global medical and socioeconomic problem characterized by leg or back pain, weakness in the lower extremities and paresthesia. OBJECTIVES: A multicenter, randomized, double-blinded, parallel, positive-controlled clinical trial was conducted to evaluate the efficacy and safety of Yaobitong capsules (YBT) for LDH. MATERIAL AND METHODS: Patients (n = 479) were recruited and randomized into YBT and Jingyaokang capsule (JYK) groups (the positive control), and received YBT or JYK at a dose of 3 capsules 3 times per day after a meal for 30 days. The primary efficacy outcome was the Oswestry Disability Index (ODI), with the visual analogue scale (VAS) used as the secondary efficacy outcome. The adverse events and adverse reactions were also evaluated. RESULTS: There was no significant difference in baseline characteristics between YBT (n = 358) and JYK groups (n = 120), and no difference was observed between groups for mean ODI score at day 0 (p = 0.064) or day 7 (p = 0.196), but there were differences at days 14, 21 and 30 (p < 0.001). The YBT showed more decline from baseline, and the decreased ODI score was substantially different from JYK (p < 0.001). The differences in decreased VAS scores between YBT and JYK were also significant at each time point (days 7, 14, 21, and 30), with better scores in the YBT group than in the JYK group (p < 0.001). In terms of safety, there was no obvious disparity in adverse events or adverse reactions between the 2 groups (p > 0.05). CONCLUSIONS: Yaobitong was better than JYK for LDH treatment, with no significant difference in safety. The study suggests that YBT is a promising and effective treatment for LDH.

Association between particulate air pollution and hypertensive disorders in pregnancy: A retrospective cohort study.

BACKGROUND: Epidemiological findings regarding the association of particulate matter ≤2.5 µm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy. METHODS AND FINDINGS: A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly PM2.5 exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 µg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochran's Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP. CONCLUSIONS: Our findings add to the literature on associations between air pollution exposure and HDP. To our knowledge, this is the first study reporting that specific air pollution components, mixture effects, and susceptible windows of PM2.5 may affect GH and PE-E differently.

20-year depressive symptoms, dementia, and structural neuropathology in older women.

INTRODUCTION: The course of depressive symptoms and dementia risk is unclear, as are potential structural neuropathological common causes. METHODS: Utilizing joint latent class mixture models, we identified longitudinal trajectories of annually assessed depressive symptoms and dementia risk over 21 years in 957 older women (baseline age 72.7 years old) from the Women's Health Initiative Memory Study. In a subsample of 569 women who underwent structural magnetic resonance imaging, we examined whether estimates of cerebrovascular disease and Alzheimer's disease (AD)-related neurodegeneration were associated with identified trajectories. RESULTS: Five trajectories of depressive symptoms and dementia risk were identified. Compared to women with minimal symptoms, women who reported mild and stable and emerging depressive symptoms were at the highest risk of developing dementia and had more cerebrovascular disease and AD-related neurodegeneration. DISCUSSION: There are heterogeneous profiles of depressive symptoms and dementia risk. Common neuropathological factors may contribute to both depression and dementia. Highlights The progression of depressive symptoms and concurrent dementia risk is heterogeneous. Emerging depressive symptoms may be a prodromal symptom of dementia. Cerebrovascular disease and AD are potentially shared neuropathological factors.

Repeatability assessment of anterior segment measurements in myopic patients using an anterior segment OCT with placido corneal topography and agreement with a swept-source OCT.

BACKGROUND: The precision of anterior segment biometric measurements in eyes has become increasingly important in refractive surgery. The purpose of this study is to assess the repeatability of the automatic measurements provided by a new spectral-domain optical coherence tomograph (SD-OCT)/Placido topographer (MS-39, CSO) and its agreement with a swept-source OCT (SS-OCT) biometer (CASIA SS-1000, Tomey) in patients with myopia. METHODS: The right eye of 235 subjects was scanned 3 times with both devices. The evaluated parameters included central corneal radius of the steep meridian, central corneal radius of the flat meridian, mean central corneal radius, thinnest corneal thickness, central corneal thickness, anterior chamber depth, corneal volume and diameter. The intraobserver repeatability of the MS-39 measurements was calculated using intraclass correlation coefficient (ICC), within subject standard deviation, coefficient of repeatability, coefficient of variation and repeated-measures analysis of variance of the 3 repeated measurements. The agreement between the two devices was evaluated by 95% limits of agreement (LoA). RESULTS: The majority of the parameters acquired from MS-39 showed high repeatability. The repeatability of corneal diameter was slightly lower than the other measurements, although the ICC remained high. Agreement with the CASIA SS-1000 was good, indicated by the Bland-Altman plots with narrow 95% LoA values for all parameters assessed. CONCLUSIONS: The high repeatability of automatic measurements by the new device supports its clinical application in eyes with myopia, and the good agreement between the two devices indicates they could be used interchangeably for the parameters evaluated.

The Impact of Modified Body Mass Index on Clinical Prognosis in the Elderly With Acute Ischemic Stroke.

OBJECTIVES: The modified body mass index (mBMI) combines the body mass index and serum albumin, accurately reflecting the nutritional status. It remains uncertain whether modified body mass index influences neurological function and clinical prognosis in elderly patients with acute ischemic stroke. METHODS: We divided the cohort into quartiles of mBMI (1 to 4). The primary outcome was analyzed using the percentage of patients with a 90-day modified Rankin scale (mRS) score of 0 to 1. There were 7 secondary outcomes, including the disability level at 90 days and the National Institute of Health Stroke Scale (NIHSS) score at 14 and 90 days. RESULTS: mBMI was negatively associated with clinical prognosis at 90-day mRS score in the primary outcome (ß=-0.167; 95% CI -0.311 to 0.023, P=0.023). Moreover, mBMI1 (<896.72) and primary outcomes (ß=0.438; 95% CI: -0.018 to 0.894) were positively correlated with higher mBMI. Moreover, the number and percentage of patients completing all the duties and activities are also higher. Age-adjusted Charlson comorbidity index (aCCI) and posterior circulation lesion were positively associated with the clinical prognosis 90-day mRS score in the primary outcome (ß=2.218; 95% CI: 1.144-4.300, ß=2.771; 95% CI: 1.700-4.516). However, BMI and serum albumin were not associated the with clinical prognosis primary outcome. BMI negatively correlates with secondary outcomes (NIHSS at discharge, ß=-0.023; 95% CI: -0.102 to 0.057). CONCLUSIONS: Our study revealed that mBMI and not BMI could be a better primary outcome predictor in the elderly with acute ischemic stroke, and lower mBMI showed a worse prognosis.

Olfactory deficit: a potential functional marker across the Alzheimer's disease continuum.

Alzheimer's disease (AD) is a prevalent form of dementia that affects an estimated 32 million individuals globally. Identifying early indicators is vital for screening at-risk populations and implementing timely interventions. At present, there is an urgent need for early and sensitive biomarkers to screen individuals at risk of AD. Among all sensory biomarkers, olfaction is currently one of the most promising indicators for AD. Olfactory dysfunction signifies a decline in the ability to detect, identify, or remember odors. Within the spectrum of AD, impairment in olfactory identification precedes detectable cognitive impairments, including mild cognitive impairment (MCI) and even the stage of subjective cognitive decline (SCD), by several years. Olfactory impairment is closely linked to the clinical symptoms and neuropathological biomarkers of AD, accompanied by significant structural and functional abnormalities in the brain. Olfactory behavior examination can subjectively evaluate the abilities of olfactory identification, threshold, and discrimination. Olfactory functional magnetic resonance imaging (fMRI) can provide a relatively objective assessment of olfactory capabilities, with the potential to become a promising tool for exploring the neural mechanisms of olfactory damage in AD. Here, we provide a timely review of recent literature on the characteristics, neuropathology, and examination of olfactory dysfunction in the AD continuum. We focus on the early changes in olfactory indicators detected by behavioral and fMRI assessments and discuss the potential of these techniques in MCI and preclinical AD. Despite the challenges and limitations of existing research, olfactory dysfunction has demonstrated its value in assessing neurodegenerative diseases and may serve as an early indicator of AD in the future.

Convergent and divergent genes expression profiles associated with brain-wide functional connectome dysfunction in deficit and non-deficit schizophrenia.

Deficit schizophrenia (DS) is a subtype of schizophrenia characterized by the primary and persistent negative symptoms. Previous studies have identified differences in brain functions between DS and non-deficit schizophrenia (NDS) patients. However, the genetic regulation features underlying these abnormal changes are still unknown. This study aimed to detect the altered patterns of functional connectivity (FC) in DS and NDS and investigate the gene expression profiles underlying these abnormal FC. The study recruited 82 DS patients, 96 NDS patients, and 124 healthy controls (CN). Voxel-based unbiased brain-wide association study was performed to reveal altered patterns of FC in DS and NDS patients. Machine learning techniques were used to access the utility of altered FC for diseases diagnosis. Weighted gene co-expression network analysis (WGCNA) was employed to explore the associations between altered FC and gene expression of 6 donated brains. Enrichment analysis was conducted to identify the genetic profiles, and the spatio-temporal expression patterns of the key genes were further explored. Comparing to CN, 23 and 20 brain regions with altered FC were identified in DS and NDS patients. The altered FC among these regions showed significant correlations with the SDS scores and exhibited high efficiency in disease classification. WGCNA revealed associations between DS/NDS-related gene expression and altered FC. Additionally, 22 overlapped genes, including 12 positive regulation genes and 10 negative regulation genes, were found between NDS and DS. Enrichment analyses demonstrated relationships between identified genes and significant pathways related to cellular response, neuro regulation, receptor binding, and channel activity. Spatial and temporal gene expression profiles of SCN1B showed the lowest expression at the initiation of embryonic development, while DPYSL3 exhibited rapid increased in the fetal. The present study revealed different altered patterns of FC in DS and NDS patients and highlighted the potential value of FC in disease classification. The associations between gene expression and neuroimaging provided insights into specific and common genetic regulation underlying these brain functional changes in DS and NDS, suggesting a potential genetic-imaging pathogenesis of schizophrenia.

Repetitive transcranial magnetic stimulation regulates effective connectivity patterns of brain networks in the spectrum of preclinical Alzheimer's disease.

Objectives: Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered as the spectrum of preclinical Alzheimer's disease (AD), with abnormal brain network connectivity as the main neuroimaging feature. Repetitive transcranial magnetic stimulation (rTMS) has been proven to be an effective non-invasive technique for addressing neuropsychiatric disorders. This study aims to explore the potential of targeted rTMS to regulate effective connectivity within the default mode network (DMN) and the executive control network (CEN), thereby improving cognitive function. Methods: This study included 86 healthy controls (HCs), 72 SCDs, and 86 aMCIs. Among them, 10 SCDs and 11 aMCIs received a 2-week rTMS course of 5-day, once-daily. Cross-sectional analysis with the spectral dynamic causal model (spDCM) was used to analyze the DMN and CEN effective connectivity patterns of the three groups. Afterwards, longitudinal analysis was conducted on the changes in effective connectivity patterns and cognitive function before and after rTMS for SCD and aMCI, and the correlation between them was analyzed. Results: Cross-sectional analysis showed different effective connectivity patterns in the DMN and CEN among the three groups. Longitudinal analysis showed that the effective connectivity pattern of the SCD had changed, accompanied by improvements in episodic memory. Correlation analysis indicated a negative relationship between effective connectivity from the left angular gyrus (ANG) to the anterior cingulate gyrus and the ANG.R to the right middle frontal gyrus, with visuospatial and executive function, respectively. In patients with aMCI, episodic memory and executive function improved, while the effective connectivity pattern remained unchanged. Conclusion: This study demonstrates that PCUN-targeted rTMS in SCD regulates the abnormal effective connectivity patterns in DMN and CEN, thereby improving cognition function. Conversely, in aMCI, the mechanism of improvement may differ. Our findings further suggest that rTMS is more effective in preventing or delaying disease progression in the earlier stages of the AD spectrum. Clinical Trial Registration: http://www.chictr.org.cn, ChiCTR2000034533.

Insights into the differential molecular response of non-germinated and germinated spores of Ameson portunus in vitro by comparative transcriptome analysis.

Ameson portunus, the recently discovered causative agent of "toothpaste disease" of pond-cultured swimming crabs in China has caused enormous economic losses in aquaculture. Understanding the process of spore germination is helpful to elucidate the molecular mechanism of its invasion of host cells. Here, we obtained mature and germinating spores by isolation and purification and in vitro stimulation, respectively. Then, non-germinated and germinated spores were subjected to the comparative transcriptomic analysis to disclose differential molecular responses of these two stages. The highest germination rate, i.e., 71.45 %, was achieved in 0.01 mol/L KOH germination solution. There were 9,609 significantly differentially expressed genes (DEGs), with 685 up-regulated and 8,924 down-regulated DEGs. The up-regulated genes were significantly enriched in ribosome pathway, and the down-regulated genes were significantly enriched in various metabolic pathways, including carbohydrate metabolism, amino acid metabolism and other metabolism. The results suggested that spores require various carbohydrates and amino acids as energy to support their life activities during germination and synthesize large amounts of ribosomal proteins to provide sites for DNA replication, transcription, translation and protein synthesis of the spores of A. portunus within the host cells. Functional genes related to spore germination, such as protein phosphatase CheZ and aquaporin, were also analyzed. The analysis of transcriptome data and identification of functional genes will help to understand the process of spore germination and invasion.

SLC7A8 overexpression inhibits the growth and metastasis of lung adenocarcinoma and is correlated with a dismal prognosis.

BACKGROUND: Overexpression of solute carrier family 7 member 8 (SLC7A8) has been shown to relate to the survival time and tumor progression in cancer patients. However, the role of SLC7A8 in lung adenocarcinoma (LUAD) is still obscure. METHOD: The relationships between SLC7A8 expression in LUAD tissues and clinical values as well as immune infiltration were explored through bioinformatics. The functions and pathways of SLC7A8 in LUAD were investigated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Gene Set Enrichment Analysis, Western blotting, and other methods. RESULTS: We found that the expression of SLC7A8 was decreased significantly in LUAD tissues compared with normal tissues, which was related to the dismal survival time and disease progression. Moreover, it carried diagnostic value in LUAD and was a risk factor for dismal prognosis. Receiver operating characteristic curve analysis indicated that the expression level of SLC7A8 carried significant diagnostic value in LUAD. Overexpression of SLC7A8 inhibited the proliferation, invasion, and migration of LUAD cells, likely through a mechanism involving the cell cycle. SLC7A8 expression in LUAD was significantly correlated with the infiltration of immune cells, especially B cells, interstitial dendritic cells, mast cells, CD56 bright cells, natural killer cells, plasmacytoid dendritic cells, T follicular helper cells, T helper 2 and 17 cells, and immune factors. CONCLUSION: The downregulation of SLC7A8 was related to a dismal prognosis and immune cell infiltration in LUAD. Increasing the expression of SLC7A8 inhibited the growth and migration of LUAD cells, thereby improving the prognosis of patients.

Comparison of PM2.5 Air Pollution Exposures and Health Effects Associations Using 11 Different Modeling Approaches in the Women's Health Initiative Memory Study (WHIMS).

BACKGROUND: Many approaches to quantifying air pollution exposures have been developed. However, the impact of choice of approach on air pollution estimates and health-effects associations remains unclear. OBJECTIVES: Our objective is to compare particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) concentrations and resulting health effects associations using multiple estimation approaches previously used in epidemiologic analyses. METHODS: We assigned annual PM2.5 exposure estimates from 1999 to 2004 derived from 11 different approaches to Women's Health Initiative Memory Study (WHIMS) participant addresses within the contiguous US. Approaches included geostatistical interpolation approaches, land-use regression or spatiotemporal models, satellite-derived approaches, air dispersion and chemical transport models, and hybrid models. We used descriptive statistics and plots to assess relative and absolute agreement among exposure estimates and examined the impact of approach on associations between PM2.5 and death due to natural causes, cardiovascular disease (CVD) mortality, and incident CVD events, adjusting for individual-level covariates and climate-based region. RESULTS: With a few exceptions, relative agreement of approach-specific PM2.5 exposure estimates was high for PM2.5 concentrations across the contiguous US. Agreement among approach-specific exposure estimates was stronger near PM2.5 monitors, in certain regions of the country, and in 2004 vs. 1999. Collectively, our results suggest but do not quantify lower agreement at local spatial scales for PM2.5. There was no evidence of large differences in health effects associations with PM2.5 among estimation approaches in analyses adjusted for climate region. CONCLUSIONS: Different estimation approaches produced similar spatial patterns of PM2.5 concentrations across the contiguous US and in areas with dense monitoring data, and PM2.5-health effects associations were similar among estimation approaches. PM2.5 estimates and PM2.5-health effects associations may differ more in samples drawn from smaller areas or areas without substantial monitoring data, or in analyses with finer adjustment for participant location. Our results can inform decisions about PM2.5 estimation approach in epidemiologic studies, as investigators balance concerns about bias, efficiency, and resource allocation. Future work is needed to understand whether these conclusions also apply in the context of other air pollutants of interest. https://doi.org/10.1289/EHP12995.

Adsorption of Zn(II) from aqueous solution and separation of zinc isotopes by displacement chromatography using chelating adsorbent.

The removal of zinc ions (Zn(II)) in water and the separation of zinc isotopes were fully investigated in this study. Imidodiacetic acid (IDA) type adsorbent (named PSGI) based on polystyrene spheres (PS) was synthesized by simultaneous irradiation grafting. By adsorption method, the removal of Zn(II) from water by the chelating adsorbent was studied in batch experiments. Under optimized condition, PSGI showed the removal efficiency of more than 98 % for Zn(II) and the adsorption capacity of 70.1 mg/g. Langmuir isothermal and pseudo-second-order kinetic model fitted the experimental results better, indicating that the adsorption is dominated by chemical adsorption. The spent adsorbent (PSGI-Zn) was used for further zinc isotope separation by displacement chromatography using EDTA-NH4 solution as eluent. Due to the mass effect of isotopes, 70Zn was found to preferentially fractionated into the front-end effluents with the highest front enrichment values of 70Zn/64Zn. By extending the migration distance to 20 m, we obtained the best isotope enrichment with the front maximum enrichment values as 1.0949, 1.0739 and separation coefficient values as 1.977 × 10-3, 8.33 × 10-3 corresponding to the isotope pairs 66Zn/64Zn, 68Zn/64Zn.

Neighborhood Disadvantage and Autism Spectrum Disorder in a Population With Health Insurance.

Importance: Family socioeconomic status has been associated with autism spectrum disorder (ASD) diagnoses. Less is known regarding the role of neighborhood disadvantage in the United States, particularly when children have similar access to health insurance. Objective: To evaluate the association between neighborhood disadvantage and the diagnosis of ASD and potential effect modification by maternal and child demographic characteristics. Design, Setting, and Participants: This cohort study examined a retrospective birth cohort from Kaiser Permanente Southern California (KPSC), an integrated health care system. Children born in 2001 to 2014 at KPSC were followed up through KPSC membership records. Electronic medical records were used to obtain an ASD diagnosis up to December 31, 2019, or the last follow-up. Data were analyzed from February 2022 to September 2023. Exposure: Socioeconomic disadvantage at the neighborhood level, an index derived from 7 US census tract characteristics using principal component analysis. Main Outcomes and Measures: Clinical ASD diagnosis based on electronic medical records. Associations between neighborhood disadvantage and ASD diagnosis were determined by hazard ratios (HRs) from Cox regression models adjusted for birth year, child sex, maternal age at delivery, parity, severe prepregnancy health conditions, maternal race and ethnicity, and maternal education. Effect modification by maternal race and ethnicity, maternal education, and child sex was assessed. Results: Among 318 372 mothers with singleton deliveries during the study period, 6357 children had ASD diagnoses during follow-up; their median age at diagnosis was 3.53 years (IQR, 2.57-5.34 years). Neighborhood disadvantage was associated with a higher likelihood of ASD diagnosis (HR, 1.07; 95% CI, 1.02-1.11, per IQR = 2.70 increase). Children of mothers from minoritized racial and ethnic groups (African American or Black, Asian or Pacific Islander, Hispanic or Latinx groups) had increased likelihood of ASD diagnosis compared with children of White mothers. There was an interaction between maternal race and ethnicity and neighborhood disadvantage (difference in log-likelihood = 21.88; P < .001 for interaction under χ24); neighborhood disadvantage was only associated with ASD among children of White mothers (HR, 1.17; 95% CI, 1.09-1.26, per IQR = 2.00 increase). Maternal education and child sex did not significantly modify the neighborhood-ASD association. Conclusions and Relevance: In this study, children residing in more disadvantaged neighborhoods at birth had higher likelihood of ASD diagnosis among a population with health insurance. Future research is warranted to investigate the mechanisms behind the neighborhood-related disparities in ASD diagnosis, alongside efforts to provide resources for early intervention and family support in communities with a higher likelihood of ASD.

Non-alcoholic fatty liver disease is associated with brain function disruption in type 2 diabetes patients without cognitive impairment.

AIMS: To investigate the neural static and dynamic intrinsic activity of intra-/inter-network topology among patients with type 2 diabetes (T2D) with non-alcoholic fatty liver disease (NAFLD) and those without NAFLD (T2NAFLD group and T2noNAFLD group, respectively) and to assess the relationship with metabolism. METHODS: Fifty-six patients with T2NAFLD, 78 with T2noNAFLD, and 55 healthy controls (HCs) were recruited to the study. Participants had normal cognition and underwent functional magnetic resonance imaging scans, clinical measurements, and global cognition evaluation. Independent component analysis was used to identify frequency spectrum parameters, static functional network connectivity, and temporal properties of dynamic functional network connectivity (P < 0.05, false discovery rate-corrected). Statistical analysis involved one-way analysis of covariance with post hoc, partial correlation and canonical correlation analyses. RESULTS: Our findings showed that: (i) T2NAFLD patients had more disordered glucose and lipid metabolism, had more severe insulin resistance, and were more obese than T2noNAFLD patients; (ii) T2D patients exhibited disrupted brain function, as evidenced by alterations in intra-/inter-network topology, even without clinically measurable cognitive impairment; (iii) T2NAFLD patients had more significant reductions in the frequency spectrum parameters of cognitive executive and visual networks than those with T2noNAFLD; and (iv) altered brain function in T2D patients was correlated with postprandial glucose, high-density lipoprotein cholesterol, and waist-hip ratio. CONCLUSION: This study may provide novel insights into neuroimaging correlates for underlying pathophysiological processes inducing brain damage in T2NAFLD. Thus, controlling blood glucose levels, lipid levels and abdominal obesity may reduce brain damage risk in such patients.

Differential molecular responses of hemolymph and hepatopancreas of swimming crab, Portunus trituberculatus, infected with Ameson portunus (Microsporidia).

Ameson portunus (Microsporidia) has caused serious economic losses to the aquaculture industry of swimming crab, Portunus trituberculatus. The hemolymph and hepatopancreas are the main immune organs of P. trituberculatus, and the main sites of A. portunus infection. Elucidating the response characteristics of hemolymph and hepatopancreas to microsporidian infection facilitates the development of microsporidiosis prevention and control strategy. This study performed comparative transcriptomic analysis of hemolymph (PTX/PTXA) and hepatopancreas (PTG/PTGA) of P. trituberculatus uninfected and infected with A. portunus. The results showed that there were 223 and 1309 differentially expressed genes (DEGs) in PTX/PTXA and PTG/PTGA, respectively. The lysosome pathway was significantly enriched after the invasion of the hemolymph by A. portunus. Also, immune-related genes were all significantly up-regulated in the hemolymph and hepatopancreas, suggesting that the invasion by A. portunus may activate host immune responses. Unlike hemolymph, antioxidant and detoxification-related genes were also significantly up-regulated in the hepatopancreas. Moreover, metabolism-related genes were significantly down-regulated in the hepatopancreas, suggesting that energy synthesis, resistance to pathogens, and regulation of oxidative stress were suppressed in the hepatopancreas. Hemolymph and hepatopancreas have similarity and tissue specificity to microsporidian infection. The differential genes and pathways identified in this study can provide references for the prevention and control of microsporidiosis.

Single-neuron analysis of axon arbors reveals distinct presynaptic organizations between feedforward and feedback projections.

The morphology and spatial distribution of axon arbors and boutons are crucial for neuron presynaptic functions. However, the principles governing their whole-brain organization at the single-neuron level remain unclear. We developed a machine-learning method to separate axon arbors from passing axons in single-neuron reconstruction from fluorescence micro-optical sectioning tomography imaging data and obtained 62,374 axon arbors that displayed distinct morphology, spatial patterns, and scaling laws dependent on neuron types and targeted brain areas. Focusing on the axon arbors in the thalamus and cortex, we revealed the segregated spatial distributions and distinct morphology but shared topographic gradients between feedforward and feedback projections. Furthermore, we uncovered an association between arbor complexity and microglia density. Finally, we found that the boutons on terminal arbors show branch-specific clustering with a log-normal distribution that again differed between feedforward and feedback terminal arbors. Together, our study revealed distinct presynaptic structural organizations underlying diverse functional innervation of single projection neurons.